浅析陈实功治疡疾以脾胃为要

陈实功为明代著名外科医家,是中医外科学三大流派之一正宗派创始人,其"脾胃为要"的学术思想贯穿疡疾治疗的始终。陈实功认为疡疾的发生、发展及预后转归与脾胃关系密切,脾胃功能受损,可导致疡疾为患。治疗疡疾时当以"初期宜消,慎伤脾胃;将溃宜托,健运脾胃;溃后宜补,强壮脾胃"为治疗法则,日常调护也应注重脾胃,慎用寒凉以免损及脾胃。

Two-sample Mendelian randomization analysis of causal relationship between eczema and autoimmune diseases

Objective:The causal relationship between eczema and autoimmune diseases has not been previously reported.This study aims to evaluate the causal relationship between eczema and autoimmune diseases.Methods:The two‐sample Mendelian randomization(MR)method was used to assess the causal effect of eczema on autoimmune diseases.Summary data from the Genome-Wide Association Study Catalog(GWAS)were obtained from the Integrative Epidemiology Unit(IEU)database.For eczema and autoimmune diseases,genetic instrument variants(GIVs)were identified according to the significant difference(P<5×10−8).Causal effect estimates were generated using the inverse‐variance weighted(IVW)method.MR Egger,maximum likelihood,MR-PRESSO,and MR-RAPS methods were used for alternative analyses.Sensitivity tests,including heterogeneity,horizontal pleiotropy,and leave-one-out analyses,were performed.Finally,reverse causality was assessed.Results:Genetic susceptibility to eczema was associated with an increased risk of Crohn’s disease(OR=1.444,95%CI 1.199 to 1.738,P<0.001)and ulcerative colitis(OR=1.002,95%CI 1.001 to 1.003,P=0.002).However,no causal relationship was found for the other 6 autoimmune diseases,including systemic lupus erythematosus(SLE)(OR=0.932,P=0.401),bullous pemphigoid(BP)(OR=1.191,P=0.642),vitiligo(OR=1.000,P=0.327),multiple sclerosis(MS)(OR=1.000,P=0.965),ankylosing spondylitis(AS)(OR=1.001,P=0.121),rheumatoid arthritis(RA)(OR=1.000,P=0.460).Additionally,no reverse causal relationship was found between autoimmune diseases and eczema.Conclusion:Eczema is associated with an increased risk of Crohn’s disease and ulcerative colitis.No causal relationship is found between eczema and SLE,MS,AS,RA,BP,or vitiligo.

Association Between Genital Ulcer Disease and HIV Seroprevalence among STD Patients in Guangzhou

Objectives: To understand genital ulcer disease(GUD) among patients attending sexually transmitteddisease (STD) clinics in Guangzhou, China, and itsassociation with HIV infection.Methods: Between September 9th, 1997 and Octo-ber 30th, 2002, 8 962 patients with STDs wereevaluated. 285 patients were diagnosed with GUD basedon clinical manifestations and microbiologic evalua-tions including dark field microscopy and serologytest for syphilis (RPR, TPPA). Swabs of each genitalulcer were processed in a multiplex PCR assay (M-PCR) for simultaneous detection of Herpes simplexvirus (HSV), Treponema pallium, and Haemophilusducreyi. Other STDs were classified by routine diag-nostic criteria, including microscopy or culture forNeisseria gonorrhoeae, Chlamydia trachomatis,Urea- plasma urealyticum, Human papillomavirus,Trichomonas, etc.Results: Of the 8 962 patients with STDs, the HIVseroprevalence in patients with and without GUD was1.75% (5/285) and 1.53% (133/8677), respectively,with no statistically significant difference (χ 2=0.09,P>0.05; OR=1.15, 95%CI=0.47-2.81) . HIVseroprevalence in patients with syphilis, genital her-pes and other STDs was 2.81% (22/784), 0.74% (6/814) and 1.49% (110/7 364), respectively. Prevalencein patients with syphilis was significantly higher thanthat in patients with genital herpes and other STDs,(χ 2=9.92, P<0.005, OR=3.89, 95%CI=1.67-9.05;χ 2=7.66, P<0.001, OR=1.90, 95%CI=1.21-3.00).Conclusions: The study shows that the HIV sero-prevalence in this population of patients with GUDis very low. The results also indicate an associationbetween syphilis and HIV infection. The relationshipbetween genital herpes and HIV infection needsfurther research.

Expression of matrix metalloproteinase-1 and tissue inhibitor of metalloproteinase-1 in ulcerative colitis

AIM: To examine the expression of metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in the colonic mucosa of patients with ulcer- ative colitis (UC). METHODS: Reverse transcription-polymerase chain re- action (RT-PCR) and immunohistochemistry were used to study the expression of MMP-1 and TIMP-1 at both mRNA and protein levels in patients with UC and con- trols. The relationship between MMP-1 mRNA, TIMP-1 mRNA, MMP-1 mRNA/TIMP-1 mRNA ratio and the sever- ity of clinical symptoms of the patients with UC were also analyzed. RESULTS: The expression of MMP-1 mRNA and TIMP-1 mRNA in the ulcerated and inflamed colonic mucosa was signifi cantly higher than that in the non-inflamed colonic mucosa (P < 0.001), but there was no statistically signif i- cant difference in the non-inflamed colonic mucosa of UC patients and normal controls (P > 0.05). The mRNA ex- pression of MMP-1 and TIMP-1 in ulcerated colonic mu- cosa of UC patients was increased by 80-fold and 2.2-fold, respectively when compared with the normal controls. In the inflamed colonic mucosa, the increase was 30-fold and 1.6-fold, respectively. Immunohistochemical analy- sis showed that among the ulcerated, inflamed, and non-inflamed colonic mucosae of UC patients and the normal controls, the positive rate of MMP-1 expression was 87%, 87%, 40% and 35% respectively, and the positive rate of TIMP-1 expression was 89%, 89%, 80% and 75%, respectively. Furthermore, the expression of MMP-1 mRNA, TIMP-1 mRNA and the MMP-1 mRNA/ TIMP-1 mRNA ratio were correlated with the severity of clinical symptoms (P <0.05).CONCLUSION: Excessive expression of MMP-1 in the diseased colonic mucosa causes excessive hydrolysis of the extracellular matrix (ECM) and ulceration in UC pa-tients. MMP-1 mRNA, TIMP-1 mRNA and MMP-1 mRNA/ TIMP-1 mRNA ratio can be used as biomarkers to judge the severity of clinical symptoms in patients with UC. Exogenous TIMP-1 or MMP-1 inhibitor therapy is a novel treatment for patients with UC.

Dynamic functional and ultrastructural changes of gastric parietal cells induced by water immersion-restraint stress in rats

AIM： To investigate the dynamic functional and ultrastructural changes of gastric parietal cells induced by water immersion-restraint stress （WRS） in rats.METHODS： WRS model of Sprague-Dawley （SD） rats was established. Fifty-six male SD rats were randomly divided into control group, stress group and post-stress group. The stress group was divided into 1, 2 and 4 h stress subgroups. The post-stress group was divided into 24, 48 and 72 h subgroups. The pH value of gastric juice, ulcer index （UI） of gastric mucosa and H^＋, K^＋- ATPase activity of gastric parietal cells were measured. Ultrastructural change of parietal cells was observed under transmission electron microscope （TEM）.RESULTS： The pH value of gastric juice decreased time-dependently in stress group and increased in post-stress group. The H^＋, K^＋-ATPase activity of gastric parietal cells and the UI of gastric mucosa increased time-dependently in stress group and decreased in poststress group. Compared to control group, the pH value decreased remarkably （P = 0.0001）, the UI and H^＋, K^＋- ATPase activity increased significantly （P = 0.0001, P = 0.0174） in 4 h stress subgroup. UI was positively related with stress time （r = 0.9876, P 〈 0.01） but negatively with pH value （r = -0.8724, P 〈 0.05）. The parietal cells became active in stress group, especially in 4 h stress subgroup, in which plenty of intracellular canalicular and mitochondria were observed under TEM. In post-stress group, the parietal cells recovered to resting state.CONCOUSION： The acid secretion of parietal cells is consistent with their ultrastructural changes during the development and healing of stress ulcer induced by WRS and the degree of gastric mucosal lesions, suggesting gastric acid play an important role in the development of stress ulcer and is closely related with the recovery of gastric mucosal lesions induced by WRS.

Association between cag-pathogenicity island in Helicobacter pylori isolates from peptic ulcer,gastric carcinoma,and non-ulcer dyspepsia subjects with histological changes

AIM： To investigate the presence of the cag-pathogenicity island and the associated histological damage caused by strains with complete cag-PAI and with partial deletions in correlation to the disease status. METHODS： We analyzed the complete cag-PAI of 174 representative Helicobacter pylori （H pylori ） clinical isolates obtained from patients with duodenal ulcer, gastric ulcer, gastric cancer, and non-ulcer dyspepsia using eight different oligonucleotide primers viz cagA1, cagA2, cagAP1, cagAP2, cagE, cagT, LEC-1, LEC-2 spanning five different loci of the whole cag-PAI by polymerase chain reaction （PCR）. RESULTS： The complete screening of the genes comprising the cag-PAI showed that larger proportions of subjects with gastric ulcer （97.8%） inhabited strains with complete cag-PAI, followed by gastric cancer （85.7%）, non-ulcer dyspepsia （7.1%）, and duodenal ulcer （6.9%）, significant differences were found in the percentage distribution of the genes in all the clinical groups studied. It was found that strains with complete cag-PAI were able to cause severe histological damage than with the partially deleted ones. CONCLUSION： The cag-PAI is a strong virulent marker in the disease pathogenesis as it is shown that a large number of those infected with strain with complete cag-PAI had one or the other of the irreversible gastric pathologies and interestingly 18.5% of them developed gastric carcinoma. The presence of an intact cag- PAI correlates with the development of more severe pathology, and such strains were found more frequently in patients with severe gastroduodenal disease. Partial deletions of the cag-PAI appear to be sufficient to render the organism less pathogenic.

Family and twin studies in inflammatory bowel disease

Studies examining the inheritance of inflammatory bowel disease （IBD） within different family groups have been the basis for recent molecular advances in the genetics of IBD. The derived heritability in Crohn＇s disease （CD） is higher than in many other complex diseases. The risk of IBD is highest in first-degree relatives of a CD proband, but first-degree relatives of a proband suffering from ulcerative colitis （UC） and more distant relatives are also at increased risk. Disease concordance rates in IBD have been examined in multiplex families and in three large European twin studies.

Effects of acupuncturing Tsusanli (S_T36) on expression of nitric oxide synthase in hypothalamus and adrenal gland in rats with cold stress ulcer

AIM： To study the protective effect of acupuncturing Tsusanli （ST36） on cold stress ulcer, and the expression of nitric oxide synthase （NOS） in hypothalarnus and adrenal gland. METHODS： Ulcer index in rats and RT-PCR were used to study the protective effect of acupuncture on cold stress ulcer, and the expression of NOS in hypothalamus and adrenal gland. Images were analyzed with semi-quantitative method. RESULTS： The ulcer index significantly decreased in rats with stress ulcer. Plasma cortisol concentration was up regulated during cold stress, which could be depressed by pre-acupuncture. The expression of NOS1 in hypothallamus increased after acupuncture. The increased expression of NOS2 was related with stress ulcer, which could be decreased by acupuncture. The expression of NOS3 in hypothalamus was similar to NOS2, but the effect of acupuncture was limited. The expression of NOS2 and NOS3 in adrenal gland increased after cold stress, only the expression of NOS1 could be repressed with acupuncture. There was no NOS2 expression in adrenal gland in rats with stress ulcer. CONCLUSION： The protective effect of acupuncturing Tsusanli （ST36） on the expression of NOS in hypothalamus and adrenal gland can be achieved.

Effect of fish oil enriched enteral diet on inflammatory bowel disease tissues in organ culture: Differential effects on ulcerative colitis and Crohn's disease

AIM： To investigate the influence of fish oil enriched enteral diet on intestinal tissues taken from Crohn＇s disease （CD）, ulcerative colitis （UC） and non-inflamed non-IBD control patients in vitro. METHODS： Colonoscopic biopsies from patients with active CD （n = 4）, active UC （n = 7）, and non-inflamed non-IBD control patients （n = 4） were incubated （three dilutions of 1：20, 1：10, and 1：5） with Waymouth＇s culture medium and enteral elemental diet （EO28, SHS, Liverpool, UK） modified in the fatty acid composition with fish oil （EF） in an organ culture system for 24 h. In each experimental set-up, incubation with Waymouth＇s medium alone as control was included. Tissue viability was assessed by adding bromodeoxyuridine （BrdU） to the culture fluid and immunohistochemically staining for BrdU uptake. Cytokine ratio of IL-1ra/IL-1β （low ratio indicative of inflammation） and production of those cytokines as a percentage of medium control were assayed in the culture supernatant. RESULTS： Incubation of CD-affected tissue with EF （1：20, 1：10, and 1：5） modestly and non-significantly increased IL-1ra/IL-1β ratio as compared with medium control （CD 39.1±16.1; 26.5±7.8, 47.1±16.8 vs control 13.0±2.2）, but incubation of UC-affected tissues increased IL-1ra/IL-1β ratio significantly in all three dilutions （UC 69.1±32.2, P〈0.05; 76.1±36.4, P = 0.05; 84.5±37.3, P〈0.02; vs control 10.2±3.7）. Incubation of non-inflamed non-IBD control tissue did not increase the IL-1ra/IL-1β ratio in any dilution compared to medium control （69.3±47.0, 54.1±30.6, 79.4±34.0 vs control 76.1±37.3）. Average percentage production of IL-1β indexed against medium control was significantly less in UC after EF incubation as compared with CD （UC 24.0±4.8 vs CD 51.8±8.1; P〈0.05）. Average percentage production of IL-tra was markedly higher in UC （135.9±3.4） than that in control patients （36.5±4.3） （p〈0.0001）. CONCLUSION： IBD tissues, after incubation with elemental diet modified in its fatty acid composition with fish oil, show an increase in IL-1ra/IL-1β cytokine ratio. This effect of ω-3 fatty acid modulation is significantly more marked in UC compared with CD and is accompanied by both a reduction of IL-1β and increase of IL-1ra. The positive direct anti-inflammatory effect of elemental diet with fish oil in tissue affected with UC suggests dietary treatment of UC may be possible.

Serum biomarker tests are useful in delineating between patients with gastric atrophy and normal,healthy stomach

AIM:To study the value of serum biomarker tests to differentiate between patients with healthy or diseased stomach mucosa:i.e.those with Helicobacter pylori(H pylori)gastritis or atrophic gastritis,who have a high risk of gastric cancer or peptic ulcer diseases.METHODS:Among 162 Japanese outpatients,pepsinogen-(Pg-)and(Pg)were measured using a conventional Japanese technique,and the European GastroPanel examination(Pg and Pg,gastrin-17 and H pylori antibodies).Gastroscopy with gastric biopsies was performed to classify the patients into those with healthy stomach mucosa,H pylori non-atrophic gastritis or atrophic gastritis.RESULTS:Pg-and Pg assays with the GastroPanel and the Japanese method showed a highly significant correlation.For methodological reasons,however,serum Pg-,but not Pg,was twice as high with the GastroPanel test as with the Japanese test.The biomarker assays revealed that 5%of subjects had advanced atrophic corpus gastritis which was also verified by endoscopic biopsies.GastroPanel examination revealed an additional seven patients who had either advanced atrophic gastritis limited to the antrum or antrum-predominant H pylori gastritis.When compared to the endoscopic biopsy findings,the GastroPanel examination classified the patients into groups with "healthy" or "diseased" stomach mucosa with 94% accuracy,95% sensitivity and 93% specifi city.CONCLUSION:Serum biomarker tests can be used to differentiate between subjects with healthy and diseased gastric mucosa with high accuracy.

Successful isolation of Helicobacter pylori after prolonged incubation from a patient with failed eradication therapy

Helicobacter pylori(H pylori),a gastric pathogen,is a major cause of chronic gastritis and peptic ulcer disease,and is an important risk factor for the development of gastric malignancies.Culture of the bacterium from gastric biopsy is essential for the determination of drug resistance of H pylori.However,the isolation rates of H pylori from infected individuals vary from 23.5%to 97% due to a number of factors such as biopsy preparation,cultural environment,medium and the method adopted.In the present case,we found that a prolonged incubation period of up to 19 d allowed successful isolation of H pylori from a patient who received triple therapy that failed to eradicate the bacterium.

Single nucleotide polymorphism in the tumor necrosis factor-alpha gene affects inflammatory bowel diseases risk

AIM: To investigate the role that single nucleotide polymorphisms (SNPs) in the promoter of the tumour necrosis factor-alpha (TNF-α) gene play in the risk of inflammatory bowel diseases (IBDs) in a New Zealand population, in the context of international studies. METHODS: DNA samples from 388 patients with Crohn's disease (CD), 405 ulcerative colitis (UC), 27 indeterminate colitis (IC) and 201 randomly selected controls, from Canterbury, New Zealand were screened for 3 common polymorphisms in the TNF-α receptor: -238 G→A, -308 G→A and -857C→T, using a TaqmanR assay. A meta-analysis was performed on the data obtained on these polymorphisms combined with that from other published studies. RESULTS: Individuals carrying the -308 G/A allele had a significantly (OR = 1.91, χ2 = 17.36, P < 0.0001) increased risk of pancolitis, and a 1.57-fold increased risk (OR = 1.57, χ2 = 4.34, P = 0.037) of requiring a bowel resection in UC. Carrying the -857 C/T variant decreased the risk of ileocolonic CD (OR = 0.56, χ2 =4.32, P = 0.037), and the need for a bowel resection (OR = 0.59, χ2 = 4.85, P = 0.028). The risk of UC was reduced in individuals who were smokers at diagnosis, (OR = 0.48, χ2 = 4.86, P = 0.028). CONCLUSION: TNF-α is a key cytokine known to play a role in inflammatory response, and the locus for the gene is found in the IBD3 region on chromosome 6p21, known to be associated with an increased risk for IBD. The -308 G/A SNP in the TNF-α promoter is functional, and may account in part for the increased UC risk associated with the IBD3 genomic region. The -857 C/T SNP may decrease IBD risk in certain groups. Pharmaco- or nutrigenomic approaches may be desir- able for individuals with such affected genotypes.

Replication of interleukin 23 receptor and autophagy-related 16-like 1 association in adult-and pediatric-onset inflammatory bowel disease in Italy

AIM: To investigate gene variants in a large Italian inflammatory bowel disease (IBD) cohort, and to analyze the correlation of sub-phenotypes (including age at diagnosis) and epistatic interaction with other IBD genes. METHODS: Total of 763 patients with Crohn's disease (CD, 189 diagnosed at age < 19 years), 843 with ulcerative colitis (UC, 179 diagnosed <19 years), 749 healthy controls, and 546 healthy parents (273 trios) were included in the study. The rs2241880 [autophagy-related 16-like 1 (ATG16L1)], rs11209026 and rs7517847 [interleukin 23 receptor (IL23R)], rs2066844, rs2066845, rs2066847 (CARD15), rs1050152 (OCTN1), and rs2631367 (OCTN2) gene variants were genotyped. RESULTS: The frequency of G allele of ATG16L1 SNP (Ala197Thr) was increased in patients with CD compared with controls (59% vs 54% respectively) (OR = 1.25, CI = 1.08-1.45, P = 0.003), but not in UC (55%). The frequency of A and G (minor) alleles of Arg381Gln, rs11209026 and rs7517847 variants of IL23R were reduced significantly in CD (4%, OR = 0.62, CI = 0.45-0.87, P = 0.005; 28%, OR = 0.64, CI = 0.55-0.75, P < 0.01), compared with controls (6% and 38%, respectively). The A allele (but not G) was also reduced signifi cantly in UC (4%, OR = 0.69, CI = 0.5-0.94, P = 0.019). No association was demonstrated with sub-phenotypes and interaction with CARD15 , and OCTN1/2 genes, although both gene variants were associated with pediatric-onset disease. CONCLUSION: The present study confirms the association of IL23R polymorphisms with IBD, and ATG16L1 with CD, in both adult- and pediatric-onset subsets in our study population.

Do patients with non-ulcer dyspepsia respond differently to Helicobacter pylorieradication treatments from those with peptic ulcer disease? A systematic review

AIM: It is controversial whether patients with non-ulcer dyspepsia (NUD) respond differently to Helicobacter pylori (H pylori) eradication treatment than those with peptic ulcer disease (PUD). To review the evidence for any difference in H pylorieradication rates between PUD and NUD patients. METHODS: A literature search for full articles and meeting abstracts to July 2004 was conducted. We included studies evaluating the efficacy of a proton pump inhibitor (P) or ranitidine bismuth citrate (RBC) plus two antibiotics of clarithromycin (C), amoxicillin (A), metronidazole (M), or P-based quadruple therapies for eradicating the infection. RESULTS: Twenty-two studies met the criteria. No significant difference in eradication rates was found between PUD and NUD patients when treated with 7-d RBCCA, 10-d PCA or P-based quadruple therapies. When the 7-d PCA was used, the pooled H pylori eradication rate was 82.1% (431/525) and 72.6% (448/617) for PUD and NUD patients, respectively, yielding a RR of 1.15 (95%CI 1.01-1.29). However, the statistically significant difference was seen only in meeting abstracts, but not in full publications. CONCLUSION: There is no convincing evidence to suggest that NUD patients respond to H pylori eradication treatments differently from those with PUD, although a trend exists with the 7-d PCA therapy.

Strictures, diaphragms, erosions or ulcerations of ischemic type in the colon should always prompt consideration of nonsteroidal anti-inflammatory drug-induced lesions

AIM： To investigate whether NSAIDs/ASA lesions in the colon can histologically be diagnosed on the basis of ischemic necrosis similar to biopsy-based diagnosis of NSAIDs/ASA- induced erosions and ulcers of the stomach. METHODS： In the period between 1997 and 2002, we investigated biopsy materials obtained from 611 patients （415 women, 196 men, average age 60.5 years） with endoscopic focal erosions, ulcerations, strictures or diaphragms in the colon. In the biopsies obtained from these lesions, we always established the suspected diagnosis of NSA/D-inducecl lesions whenever necroses of the ischemic type were found. Together with the histological report, we enclosed a questionnaire to investigate the use of medication. The data provided by the questionnaire were then correlated with the endoscopic findings, the location, number and nature of the lesions, and the histological findings. RESULTS： At the time of their colonoscopy, 86.1% of the patients had indeed been taking NSAID/ASA medication for years （43.9%） or months （29.5%）. The most common indication for the use of these drugs was pain （64.3%）, and the most common indication for colonoscopy was bleeding （55.5%）. Endoscopic inspection revealed multiple erosions and/or ulcers in 60.6%, strictures in 15.8%, and diaphragms in 3.0% of the patients. The lesions were located mainly in the right colon including the transverse colon （79.9%）. A separate analysis of age and sex distribution, endoscopic and histological findings for NSAIDs alone, ASA alone, combined NSAID/ASA, and for patients denying the use of such drugs, revealed no significant differences among the groups. CONCLUSION： This uncontrolled retrospective study based on the histological finding of an ischemic necrosis shows that the histologically suspected diagnosis of NSAID-induced lesions in the colon is often correct. The true diagnostic validity of this finding and the differentiation from ischemic colitis should, however, be investigated in a prospective controlled study.

Diaphragm disease compared with cryptogenic multifocal ulcerous stenosing enteritis

As the use of drugs such as nonsteroidal anti-inflammatory drugs (NSAIDs) increases,so too do gastrointestinal ulcers,bleeding,perforation and obstruction.Diaphragm disease of the small intestine is formed by submucosal fibrosis and destruction of lamina muscularis due to chronic ulceration,which corresponds to the most severe stage of NSAID enteropathy.It may lead to stricture of the small intestine.If such ulcerations and strictures in the small intestine are multiple,differential diagnosis is between diaphragm disease and cryptogenic multifocal ulcerous stenosing enteritis (CMUSE),because the gross findings of diaphragm disease are similar to those of CMUSE.We report a rare case of diaphragm disease caused by NSAID.It has been finally confirmed by capsule endoscopy and the origin of chronic obscure gastrointestinal bleeding was found to be multiple ulcers and strictures in the small intestine.After operation,we diagnosed the patient with diaphragm disease rather than CMUSE.

Thrombosis and inflammatory bowel disease-the role of genetic risk factors

Thromboembolism is a significant cause of morbidity and mortality in patients with inflammatory bowel disease （IBD）. Recent data suggest thromboembolism as a disease-specific extraintestinal manifestation of IBD, which is developed as the result of multiple interactions between acquired and genetic risk factors. There is evidence indicating an imbalance of procoagulant, anticoagulant and fibrinolitic factors predisposing in thrombosis in patients with IBD. The genetic factors that have been suggested to interfere in the thrombotic manifestations of IBD include factor V Leiden, factor Ⅱ （prothrombin, G20210A）, methylenetetrahydrofolate reductase gene mutation （MTHFR, 6777T, plasminogen activator inhibitor type 1 （PAI-1） gene mutation and factor X Ⅲ （val34leu）. In this article we review the current data and future prospects on the role of genetic risk factors in the development of thromboembolism in TBD.

Roles of histamine and its receptors in allergic and inflammatory bowel diseases

Mast cell has a long history of being recognized as an important mediator-secreting cell in allergic diseases, and has been discovered to be involved in IBD in last two decades. Histamine is a major mediator in allergic diseases, and has multiple effects that are mediated by specific surface receptors on target cells. Four types of histamine receptors have now been recognized pharmacologically and the first three are located in the gut. The ability of histamine receptor antagonists to inhibit mast cell degranulation suggests that they might be developed as a group of mast cell stabilizers. Recently, a series of experiments with dispersed colon mast cells suggested that there should be at least two pathways in man for mast cells to amplify their own activation-degranulation signals in an autocrine or paracrine manner. In a word, histamine is an important mediator in allergic diseases and IBD, its antagonists may be developed as a group of mast cell stabilizers to treat these diseases.

Rectal administration of d-alpha tocopherol for active ulcerative colitis:A preliminary report

AIM: To investigate the anti-oxidant and anti-neutrophil recruitment effects of rectal d-alpha (d-α) tocopherol administration on mild and moderately active ulcerative colitis (UC). METHODS: Fifteen patients with mild and moderately active ulcerative colitis were enrolled in an open-label study of d-α tocopherol enema (8000 U/d) for 12 wk. All patients were receiving concomitant therapy with 5-aminosalicylic acid derivatives (5-ASA) and/or immunomodulator medications. Endoscopic evaluation was performed at baseline and after 4th and 12th weeks. Disease activity was measured with the Mayo disease activity index (DAI) and remission was defined as DAI of ≤ 2 with no blood in stool. Clinical response was defined as a DAI reduction of ≥ 2. RESULTS: At the end of 12th week,the average DAI score significantly decreased compared to the beginning of the study (2.3 ± 0.37 vs 8 ± 0.48,P < 0.0001). One patient was withdrawn after 3 wk for being unavailable to follow-up. On the 4th week of therapy,12 patients showed clinical response,3 of whom (21.4%) achieving remission. After 12 wk,all 14 patients responded clinically to the therapy and remission was induced in 9 of them (64%). No patient reported adverse events or was hospitalized due to worsened disease activity. CONCLUSION: This preliminary report suggests that rectal d-α tocopherol may represent a novel therapy for mild and moderately active UC. The observed results might be due to the anti-inflammatory and anti-oxidative properties of vitamin E.